What is the recommended treatment for complicated urinary tract infections (UTIs)?

Treatment of Complicated Urinary Tract Infections (cUTIs)

For complicated urinary tract infections, empiric treatment should include broad-spectrum antibiotics such as fluoroquinolones, aminoglycosides, or extended-spectrum cephalosporins, with therapy tailored based on culture results and local resistance patterns. 1

Definition and Factors Associated with cUTIs

A complicated UTI occurs when a patient has host-related factors or specific anatomic/functional abnormalities in the urinary tract that make the infection more challenging to eradicate compared to uncomplicated infections 1.

Common factors associated with cUTIs include:

• Obstruction at any site in the urinary tract 1
• Foreign body presence (e.g., catheter, stent) 1
• Incomplete voiding 1
• Vesicoureteral reflux 1
• Recent history of instrumentation 1
• UTI in males 1
• Pregnancy 1
• Diabetes mellitus 1
• Immunosuppression 1
• Healthcare-associated infections 1
• ESBL-producing organisms 1
• Multidrug-resistant organisms 1

Microbiology of cUTIs

The microbial spectrum in cUTIs is broader than uncomplicated UTIs, with higher likelihood of antimicrobial resistance 1:

• Escherichia coli
• Proteus species
• Klebsiella species
• Pseudomonas species
• Serratia species
• Enterococcus species 1

Treatment Approach

General Principles

1. Mandatory management of underlying urological abnormality or complicating factor 1
2. Urine culture and susceptibility testing should be performed before starting therapy 1
3. Initial empiric therapy should be tailored based on culture results 1
4. Treatment duration: 7-14 days (14 days for men when prostatitis cannot be excluded) 1
   • Shorter duration (7 days) may be considered when patient is hemodynamically stable and afebrile for at least 48 hours 1

Empiric Parenteral Antimicrobial Options

For hospitalized patients with cUTIs requiring IV therapy, recommended options include:

• Fluoroquinolones:

  • Ciprofloxacin 400 mg IV twice daily 1
  • Levofloxacin 750 mg IV once daily 1

• Extended-spectrum cephalosporins:

  • Cefotaxime 2 g IV three times daily 1
  • Ceftriaxone 1-2 g IV once daily 1
  • Cefepime 1-2 g IV twice daily 1

• Penicillins with β-lactamase inhibitors:

  • Piperacillin/tazobactam 2.5-4.5 g IV three times daily 1

• Aminoglycosides:

  • Gentamicin 5 mg/kg IV once daily 1
  • Amikacin 15 mg/kg IV once daily 1

• For multidrug-resistant organisms (based on early culture results):

  • Carbapenems:
    • Imipenem/cilastatin 0.5 g IV three times daily 1
    • Meropenem 1 g IV three times daily 1
  • Newer agents:
    • Ceftolozane/tazobactam 1.5 g IV three times daily 1
    • Ceftazidime/avibactam 2.5 g IV three times daily 1
    • Cefiderocol 2 g IV three times daily 1
    • Meropenem-vaborbactam 2 g IV three times daily 1
    • Plazomicin 15 mg/kg IV once daily 1

Treatment for Specific Resistant Pathogens

For carbapenem-resistant Enterobacterales (CRE) causing cUTIs:

• Ceftazidime/avibactam 2.5 g IV every 8 hours 1
• Meropenem/vaborbactam 4 g IV every 8 hours 1
• Imipenem/cilastatin/relebactam 1.25 g IV every 6 hours 1
• Aminoglycosides: Gentamicin 5-7 mg/kg/day IV once daily or Amikacin 15 mg/kg/day IV once daily 1

For vancomycin-resistant Enterococci (VRE) causing cUTIs:

• Single dose of fosfomycin 3 g PO 1
• Nitrofurantoin 100 mg PO every 6 hours 1
• High-dose ampicillin (18-30 g IV daily in divided doses) or amoxicillin 500 mg IV/PO every 8 hours 1

For difficult-to-treat Pseudomonas aeruginosa:

• Colistin monotherapy or combination therapy 1
• Ceftolozane/tazobactam 1.5-3 g IV every 8 hours 1
• Ceftazidime/avibactam 2.5 g IV every 8 hours 1

Step-Down Oral Therapy

Once the patient improves clinically and organism susceptibilities are known, consider step-down to oral therapy:

• Levofloxacin 750 mg once daily for 5-10 days (for susceptible organisms) 2
• Ciprofloxacin 500-750 mg twice daily for 7-14 days 1
• Trimethoprim-sulfamethoxazole 160/800 mg twice daily for 14 days 1

Special Considerations

• Local resistance patterns should guide empiric therapy choices 1
• Fluoroquinolone resistance should be <10% to use as empiric therapy 1
• Carbapenems and novel broad-spectrum agents should be reserved for patients with known or suspected multidrug-resistant organisms 1
• Aminoglycoside monotherapy is only appropriate for urinary tract infections 1
• Duration of therapy should be individualized based on infection site, source control, underlying comorbidities, and initial response to therapy 1

Pitfalls to Avoid

• Failing to address the underlying anatomical or functional abnormality 1
• Using fluoroquinolones as first-line empiric therapy in areas with high resistance rates 3
• Inadequate duration of therapy, especially in males where prostatitis may be present 1
• Not adjusting therapy based on culture and susceptibility results 1
• Overlooking the possibility of multidrug-resistant organisms in patients with healthcare exposure or recent antibiotic use 3